First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study.

Abstract

PURPOSE:

Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study.

PATIENTS AND METHODS:

Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1).

RESULTS:

Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events.

CONCLUSION:

Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

• Authors: Heinz-Josef Lenz, Eric Van Cutsem, Maria Luisa Limon, Ka Yeung Mark Wong, Alain Hendlisz, Massimo Aglietta, Pilar García-Alfonso, Bart Neyns, Gabriele Luppi, Dana B Cardin, Tomislav Dragovich, Usman Shah, Sandzhar Abdullaev, Joseph Gricar, Jean-Marie Ledeine, Michael James Overman, Sara Lonardi
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 40 Issue 2 Pg. 161-170 (01 10 2022) ISSN: 1527-7755 [Electronic] United States
• PMID: 34637336 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Immune Checkpoint Inhibitors
• Ipilimumab
• Nivolumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Colorectal Neoplasms (drug therapy, genetics, immunology, mortality)
• DNA Mismatch Repair
• Disease Progression
• Female
• Humans
• Immune Checkpoint Inhibitors (adverse effects, therapeutic use)
• Ipilimumab (administration & dosage, adverse effects)
• Male
• Microsatellite Instability
• Middle Aged
• Neoplasm Metastasis
• Nivolumab (administration & dosage, adverse effects)
• Progression-Free Survival
• Time Factors
• Young Adult